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Dr Richard Chahwan

Dr Richard Chahwan

Senior Lecturer in Cancer Immunology

 3104

 +44 (0)1392 723104

 Living Systems Institute 5.09

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

Chromatin is a unique bearer of the cell’s genetic and epigenetic identity. To maintain their integrity, cells have developed an evolutionarily conserved array of pathways to maintain chromatin integrity; collectively known as the DNA damage response (DDR). Adequate DDR signaling in the context of chromatinized DNA requires both genetic and epigenetic modifications. Failure to do so compromises genomic stability and could lead to developmental defects and cancer.

Exceptions to this general rule, whereby certain cell types deliberately orchestrate the generation of DNA damage to mediate germline or somatic diversity, offer a highly tractable experimental and clinical approach to understand the mechanisms governing DDR. An example of this process is the initiation of somatic hypermutation and recombinqation by the potent DNA mutator AID, a member of the APOBEC family of cytosine deaminases.

My lab is interested in understanding the fundamental principles that establish the balance between maintaining chromatin integrity and generating immune diversity. We are also interested in studying the genetic and epigenetic contribution of the DDR to normal cell function and the development of various human diseases such as immunodeficiencies, autoimmunity, tumorigenesis, and aging.

Career

2016-present: Senior Lecturer in Cancer Immunology, Living Systems Institute, University of Exeter.

2013-2016: Lecturer in Molecular Immunobiology, Biosciences, University of Exeter.

2008-2013: Research Associate, Rockefeller University & Albert Einstein College of Medicine

2007: PhD Molecular Cell Biology, Gurdon Institute, University of Cambridge

 

Links

Research

Research interests

Humans and other mammals are constantly required to safeguard their genomic integrity from environmental toxins and defend themselves from lethal foreign agents. An adequate DNA damage response (DDR) achieves the former; while the latter is ensured by the acquired immune system, especially the antibody response in B cells. Interestingly, the DDR also contributes to the generation of the huge immune diversity needed to protect us against foreign antigens.


My lab is interested in understanding the fundamental principles that maintain chromatin integrity and generate immune diversity. This includes studying the complimentary role of the DDR in DNA editing through cytosine deamination.


We are also interested in studying the genetic and epigenetic contribution of the DDR to normal cell function and the development of various human diseases such as immunodeficiencies, autoimmunity, tumorigenesis, and aging.

Research grants

  • 2016 EPSRC
    EPSRC-Biosciences interdisciplinary PhD studentship
  • 2015 Royal Society Travel Grant
    International Exchange award
  • 2014 Royal Society Research Grant
    Starter Grant
  • 2014 BBSRC PhD Studentship
    PhD studentship
  • 2013 Exeter University
    Starter and SDF grants

Publications

Key publications | Publications by category | Publications by year

Key publications


Wang S, Chahwan R, Wei L, Scharff MD (In Press). Error-Prone Mismatch and Base Excision DNA Repair in Somatic Hypermutation. In  (Ed) Encyclopedia of Immunobiology, Elsevier. Abstract.
Sheppard EC, Morrish RB, Dillon MJ, Leyland R, Chahwan R (2018). Epigenomic modifications mediating antibody maturation. Frontiers in Immunology, 9(FEB). Abstract.  Full text.
Wei L, Chahwan R, Wang S, Wang X, Pham PT, Goodman MF, Bergman A, Scharff MD, MacCarthy T (2015). Overlapping hotspots in CDRs are critical sites for V region diversification. Proc Natl Acad Sci U S A, 112(7), E728-E737. Abstract.  Author URL.  Full text.
Martin A, Chahwan R, Parsa JY, Scharff MD (2014). Somatic Hypermutation: the Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. In  (Ed) Molecular Biology of B Cells: Second Edition, 363-388.  Abstract.
Van Oers JMM, Edwards Y, Chahwan R, Zhang W, Smith C, Pechuan X, Schaetzlein S, Jin B, Wang Y, Bergman A, et al (2014). The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair. Oncogene, 33(30), 3939-3946. Abstract.  Full text.
Schaetzlein S, Chahwan R, Avdievich E, Roa S, Wei K, Eoff RL, Sellers RS, Clark AB, Kunkel TA, Scharff MD, et al (2013). Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Proc Natl Acad Sci U S A, 110(27), E2470-E2479. Abstract.  Author URL.

Publications by category


Journal articles

Harmer NJ, Chahwan R (In Press). Isotype switching: Mouse IgG3 constant region drives increased affinity for polysaccharide antigens. Virulence, 7(6), 623-626. Author URL.  Full text.
Sheppard EC, Morrish RB, Dillon MJ, Leyland R, Chahwan R (2018). Epigenomic modifications mediating antibody maturation. Frontiers in Immunology, 9(FEB). Abstract.  Full text.
Wei L, Chahwan R, Wang S, Wang X, Pham PT, Goodman MF, Bergman A, Scharff MD, MacCarthy T (2015). Overlapping hotspots in CDRs are critical sites for V region diversification. Proc Natl Acad Sci U S A, 112(7), E728-E737. Abstract.  Author URL.  Full text.
Van Oers JMM, Edwards Y, Chahwan R, Zhang W, Smith C, Pechuan X, Schaetzlein S, Jin B, Wang Y, Bergman A, et al (2014). The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair. Oncogene, 33(30), 3939-3946. Abstract.  Full text.
Chahwan R, Gravel S, Matsusaka T, Jackson SP (2013). Dma/RNF8 proteins are evolutionarily conserved E3 ubiquitin ligases that target septins. Cell Cycle, 12(6), 1000-1008. Abstract.  Author URL.  Full text.
Schaetzlein S, Chahwan R, Avdievich E, Roa S, Wei K, Eoff RL, Sellers RS, Clark AB, Kunkel TA, Scharff MD, et al (2013). Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Proc Natl Acad Sci U S A, 110(27), E2470-E2479. Abstract.  Author URL.
Chahwan R, Gravel S, Matsusaka T, Jackson SP (2013). RNF8 links nucleosomal and cytoskeletal ubiquitylation of higher order protein structures. Cell Cycle, 12(8), 1161-1162. Author URL.  Full text.
Chahwan R, Edelmann W, Scharff MD, Roa S (2012). AIDing antibody diversity by error-prone mismatch repair. Semin Immunol, 24(4), 293-300. Abstract.  Author URL.
Chahwan C, Chahwan R (2012). Aicardi-Goutieres syndrome: from patients to genes and beyond. Clin Genet, 81(5), 413-420. Abstract.  Author URL.
Chahwan R, van Oers JMM, Avdievich E, Zhao C, Edelmann W, Scharff MD, Roa S (2012). The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination. J Exp Med, 209(4), 671-678. Abstract.  Author URL.  Full text.
Chahwan R, Edelmann W, Scharff MD, Roa S (2011). Mismatch-mediated error prone repair at the immunoglobulin genes. Biomed Pharmacother, 65(8), 529-536. Abstract.  Author URL.
Chahwan R, Wontakal SN, Roa S (2011). The multidimensional nature of epigenetic information and its role in disease. Discov Med, 11(58), 233-243. Abstract.  Author URL.
Chahwan R, Wontakal SN, Roa S (2010). Crosstalk between genetic and epigenetic information through cytosine deamination. Trends Genet, 26(10), 443-448. Abstract.  Author URL.
Ramachandran S, Chahwan R, Nepal RM, Frieder D, Panier S, Roa S, Zaheen A, Durocher D, Scharff MD, Martin A, et al (2010). The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proc Natl Acad Sci U S A, 107(2), 809-814. Abstract.  Author URL.
Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM, et al (2007). Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science, 318(5856), 1637-1640. Abstract.  Author URL.
McPherson JP, Lemmers B, Chahwan R, Pamidi A, Migon E, Matysiak-Zablocki E, Moynahan ME, Essers J, Hanada K, Poonepalli A, et al (2004). Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science, 304(5678), 1822-1826. Abstract.  Author URL.
Abraham J, Lemmers B, Hande MP, Moynahan ME, Chahwan C, Ciccia A, Essers J, Hanada K, Chahwan R, Khaw AK, et al (2003). Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J, 22(22), 6137-6147. Abstract.  Author URL.
Matar GM, Chahwan R, Fuleihan N, Uwaydah M, El-Hajj M, Hadi U (2002). DNA-based subtypes and antimicrobial susceptibility profiles of Haemophilus influenzae and Haemophilus parainfluenzae isolated from different tonsillar sites of children undergoing tonsillectomy and/or adenoidectomy. J Med Liban, 50(4), 157-162. Abstract.  Author URL.
Matar GM, Chahwan R, Fuleihan N, Uwaydah M, Hadi U (2001). PCR-based detection, restriction endonuclease analysis, and transcription of tonB in Haemophilus influenzae and Haemophilus parainfluenzae isolates obtained from children undergoing tonsillectomy and adenoidectomy. Clin Diagn Lab Immunol, 8(2), 221-224. Abstract.  Author URL.

Chapters

Wang S, Chahwan R, Wei L, Scharff MD (In Press). Error-Prone Mismatch and Base Excision DNA Repair in Somatic Hypermutation. In  (Ed) Encyclopedia of Immunobiology, Elsevier. Abstract.
Martin A, Chahwan R, Parsa JY, Scharff MD (2014). Somatic Hypermutation: the Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. In  (Ed) Molecular Biology of B Cells: Second Edition, 363-388.  Abstract.

Conferences

Chahwan R, Shanzhi Wang, Kyeryoung Lee, Richard Chahwan, Yongwei Zhang, Catherine Tang, Sergio Roa, Rikke B. Morrish, Elisa Pesenti, Paula E. Cohen, Thomas MacCarthy, Winfried Edelmann and Matthew Scharff (In Press). Dissecting the roles of the enzymatic and scaffolding functions of EXO1 in vivo. Cold Spring Harbour.  Abstract.

Publications by year


In Press

Chahwan R, Shanzhi Wang, Kyeryoung Lee, Richard Chahwan, Yongwei Zhang, Catherine Tang, Sergio Roa, Rikke B. Morrish, Elisa Pesenti, Paula E. Cohen, Thomas MacCarthy, Winfried Edelmann and Matthew Scharff (In Press). Dissecting the roles of the enzymatic and scaffolding functions of EXO1 in vivo. Cold Spring Harbour.  Abstract.
Wang S, Chahwan R, Wei L, Scharff MD (In Press). Error-Prone Mismatch and Base Excision DNA Repair in Somatic Hypermutation. In  (Ed) Encyclopedia of Immunobiology, Elsevier. Abstract.
Harmer NJ, Chahwan R (In Press). Isotype switching: Mouse IgG3 constant region drives increased affinity for polysaccharide antigens. Virulence, 7(6), 623-626. Author URL.  Full text.

2018

Sheppard EC, Morrish RB, Dillon MJ, Leyland R, Chahwan R (2018). Epigenomic modifications mediating antibody maturation. Frontiers in Immunology, 9(FEB). Abstract.  Full text.

2015

Wei L, Chahwan R, Wang S, Wang X, Pham PT, Goodman MF, Bergman A, Scharff MD, MacCarthy T (2015). Overlapping hotspots in CDRs are critical sites for V region diversification. Proc Natl Acad Sci U S A, 112(7), E728-E737. Abstract.  Author URL.  Full text.

2014

Martin A, Chahwan R, Parsa JY, Scharff MD (2014). Somatic Hypermutation: the Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. In  (Ed) Molecular Biology of B Cells: Second Edition, 363-388.  Abstract.
Van Oers JMM, Edwards Y, Chahwan R, Zhang W, Smith C, Pechuan X, Schaetzlein S, Jin B, Wang Y, Bergman A, et al (2014). The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair. Oncogene, 33(30), 3939-3946. Abstract.  Full text.

2013

Chahwan R, Gravel S, Matsusaka T, Jackson SP (2013). Dma/RNF8 proteins are evolutionarily conserved E3 ubiquitin ligases that target septins. Cell Cycle, 12(6), 1000-1008. Abstract.  Author URL.  Full text.
Schaetzlein S, Chahwan R, Avdievich E, Roa S, Wei K, Eoff RL, Sellers RS, Clark AB, Kunkel TA, Scharff MD, et al (2013). Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Proc Natl Acad Sci U S A, 110(27), E2470-E2479. Abstract.  Author URL.
Chahwan R, Gravel S, Matsusaka T, Jackson SP (2013). RNF8 links nucleosomal and cytoskeletal ubiquitylation of higher order protein structures. Cell Cycle, 12(8), 1161-1162. Author URL.  Full text.

2012

Chahwan R, Edelmann W, Scharff MD, Roa S (2012). AIDing antibody diversity by error-prone mismatch repair. Semin Immunol, 24(4), 293-300. Abstract.  Author URL.
Chahwan C, Chahwan R (2012). Aicardi-Goutieres syndrome: from patients to genes and beyond. Clin Genet, 81(5), 413-420. Abstract.  Author URL.
Chahwan R, van Oers JMM, Avdievich E, Zhao C, Edelmann W, Scharff MD, Roa S (2012). The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination. J Exp Med, 209(4), 671-678. Abstract.  Author URL.  Full text.

2011

Chahwan R, Edelmann W, Scharff MD, Roa S (2011). Mismatch-mediated error prone repair at the immunoglobulin genes. Biomed Pharmacother, 65(8), 529-536. Abstract.  Author URL.
Chahwan R, Wontakal SN, Roa S (2011). The multidimensional nature of epigenetic information and its role in disease. Discov Med, 11(58), 233-243. Abstract.  Author URL.

2010

Chahwan R, Wontakal SN, Roa S (2010). Crosstalk between genetic and epigenetic information through cytosine deamination. Trends Genet, 26(10), 443-448. Abstract.  Author URL.
Ramachandran S, Chahwan R, Nepal RM, Frieder D, Panier S, Roa S, Zaheen A, Durocher D, Scharff MD, Martin A, et al (2010). The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proc Natl Acad Sci U S A, 107(2), 809-814. Abstract.  Author URL.

2007

Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM, et al (2007). Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science, 318(5856), 1637-1640. Abstract.  Author URL.

2004

McPherson JP, Lemmers B, Chahwan R, Pamidi A, Migon E, Matysiak-Zablocki E, Moynahan ME, Essers J, Hanada K, Poonepalli A, et al (2004). Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science, 304(5678), 1822-1826. Abstract.  Author URL.

2003

Abraham J, Lemmers B, Hande MP, Moynahan ME, Chahwan C, Ciccia A, Essers J, Hanada K, Chahwan R, Khaw AK, et al (2003). Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J, 22(22), 6137-6147. Abstract.  Author URL.

2002

Matar GM, Chahwan R, Fuleihan N, Uwaydah M, El-Hajj M, Hadi U (2002). DNA-based subtypes and antimicrobial susceptibility profiles of Haemophilus influenzae and Haemophilus parainfluenzae isolated from different tonsillar sites of children undergoing tonsillectomy and/or adenoidectomy. J Med Liban, 50(4), 157-162. Abstract.  Author URL.

2001

Matar GM, Chahwan R, Fuleihan N, Uwaydah M, Hadi U (2001). PCR-based detection, restriction endonuclease analysis, and transcription of tonB in Haemophilus influenzae and Haemophilus parainfluenzae isolates obtained from children undergoing tonsillectomy and adenoidectomy. Clin Diagn Lab Immunol, 8(2), 221-224. Abstract.  Author URL.

Richard_Chahwan Details from cache as at 2018-12-15 18:42:34

Refresh publications

External Engagment and Impact

Editorial responsibilities

2011 - present: Editorial board member of Frontiers in Cancer Genetics, Frontiers in Biological Chemistry, Journal of Bioscience and Medicine.

2011 - present: Associate Editor of Biological and Biomedical Reports.

2011 - present: Reviewer for BBSRC, MRC, Cell Cycle, Genome research, Journal of Cell Death, Molecular Medicine, Trends in Genetics, Frontiers in Cancer Genetics, Frontiers in Biological Chemistry, Journal of Bioscience and Medicine.


Invited lectures

2016 Albert Einstein College of Medicine, New York, USA

2015 University of Bristol Medical School, Bristol, UK

2014 University of Exeter Peninsula Medical School, Exeter, UK

2012 University of London, London, UK

2012 Keystone meeting, Boston, USA

2011 University of Long Island, New York, USA

 

Teaching

I teach several courses involving various aspects of molecular and biochemical immunology.

Supervision / Group

Postdoctoral researchers

Postgraduate researchers

Research Technicians

Alumni

  • Angelina Bloch Erasmus UG exchange student
  • Praveena Deekonda Aspire UG student
  • Rikke Morrish MRes graduate
  • Hugo Parker Master Student

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